Sustained release medications are well known and are very desirable in order to permit a single dosage of medicament to remain effective over a period of time which may be up to twelve hours or more. Generally, this is accomplished by means of a gelatin capsule holding a plurality of microcapsules of medicament, each capsule being coated with a sustained release coating which permits the medicament to be slowly released through the coating of the microcapsule. Alternatively, the microcapsules may contain a plurality of different coatings so that some of the coatings dissolve almost immediately, some do not dissolve for a number of hours and some are even more stable to prevent release of medicament for many hours.
Gelatin capsules of medicament have fallen into disrepute in recent years as they are subject to tampering. Foreign substances can be placed into such gelatin capsules. Accordingly, administration forms are being sought which will avoid the use of capsules. This is particularly difficult with respect to sustained release medicaments because conventional microcapsules are known to break if subjected to the pressures required to form a tablet. If the microcapsules break, then all of the medicament is released immediately and one has no sustained release effect.
One method by which the prior art has attempted to solve this problem is described in U.S. Pat. Nos. 3,922,338 and 4,113,816. In these patents, controlled release microcapsules are formulated into a tablet by sandwiching the microcapsules between two layers of excipient in granular form which serve to cushion the microcapsules of the medial layer against the shock of compression when compressing them to tablets.
Some prior art tablets achieve sustained release by mixing the drug directly with an excipient which prevents break up of the tablets in the gastric juices or intestinal fluids so that the tablet itself slowly breaks down and releases the active principle over a period of time. For example, formulating the drug with a spongy polymer, such as methyl cellulose, will form a sustained release tablet which gradually releases drug from the polymer. Such galenical forms have the disadvantage, however, of providing high concentrations of active principle at the spot where the tablet rests which in some cases, depending on the medicament, can cause an ulcer or other complications. It is preferred that the tablet break up after administration so as to cause the active principle to disperse and not be too heavily concentrated at one place while still achieving sustained release. No simple and effective way to attain this object has yet been found in the prior art.